Funds for a cell sorter are requested to permit specialized studies at the Joslin Diabetes Center relevant to the pathogenesis of Type I and Type II diabetes mellitus, and to study one of the most serious clinical problems in diabetes, namely renal transplantation. The Joslin Diabetes Center with its Diabetes Treatment Unit and affiliation with the inpatient and transplant service at the Deaconess Hospital is an international referral center for the care of patients with diabetes, with more than 200 patients with diabetes hospitalized at any one time and more than 40,000 outpatient visits per year. This patient population base, ancillary clinical resources and a diverse diabetes research center provide more than enough patients and resources for the proposed studies. In particular, it is becoming increasingly clear that Type I diabetes is an autoimmune disease (including prevention and cure of the disease in a genetic rat model with immunotherapy) with major, but only poorly outlined T cell abnormalities. The analytic and sorting capabilities of the machine (coupled with a battery of anti-T cell monoclonals developed by Dr. Eisenbarth's and other laboratories) requested are essential to further our basic knowledge of pathogenesis and to develop improved assays to predict the development of disease in susceptible relatives. The etiology of Type II diabetes, which is not characterized by autoimmune beta cell destruction but rather by resistance to insulin action, is unknown. Exciting recent findings by Dr. Kahn of the enzymatic activity (thyrosine kinase) of the insulin receptor opens a new field for delineation of insulin action. The development of requisite cell lines with receptor deficiency and immunologic assays of the receptor is an exciting field requiring cell analyses and sorting. Patients with renal failure secondary to diabetes do poorly with any form of therapy of their end-stage disease. Further understanding of the pathogenesis of rejection in these patients as well as increased understanding of the mechanism of immunotherapy will hopefully improve the currently dismal clinical situation. For these studies cell analysis and T cell subset isolation using specific monoclonal T cell or activation (L243, 4F2, 5E9) antibodies are essential, and should be particularly useful in reference to assays of biologic function (IL-2 production and receptor acquisition) in transplant rejection.